Clinical Application Of Single Or Combinative Detection Of Multi-Tumor Markers For Diagnosis Of Ovarian Cancer And Its Staging

BackgroundOvarian cancer is one of the most common malignant tumors in the female reproductive system and present the highest mortality rate among all gynecologic tumors.However,most patients cannot be diagnosed at an early stage due to the lack of symptoms and deep in the pelvic cavity,leading to a poor prognosis.Therefore,early diagnosis is significant for the treatment and prognosis of ovarian cancer.As a non-invasive examination method,the significance of serum tumor markers for ovarian cancer screening,early diagnosis,treatment and prognosis evaluation has received extensive attention.Clinically used diagnostic markers for ovarian cancer include carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),tumor antigen 125(Cancer antigen,CA125),CA199,CA153,D-dimer and human epididymis protein 4(H4),etc.However,although the levels are elevated in most of ovarian cancer patients as reported,the specificity and sensitivity of single biomarker for the diagnosis of ovarian cancer remains questionable.Therefore,the combined detection of multiple biomarkers takes great significance for reducing the false positive rate and the rate of missed diagnosis of ovarian cancer diagnosis.ObjectsTo analyze the diagnostic efficacy of seven serum tumor markers alone or in combination in the diagnosis of ovarian cancer,and explore high sensitivity and specificity biomarkers for the diagnosis ovarian benign and malignant tumor and cancer staging,which is significant for early diagnosis,disease monitoring and prognosis prediction of ovarian cancer.MethodsThe study selected 104 patients with ovarian cancer and 101 patients with benign ovarian tumors who were first visited in our hospital from March 2015 to May 2018.The levels of serum CEA,AFP,CA199,CA153,CA125 and HE4 were measured by electro-chemiluminescence,and the D-dimer was determined by immunoturbidimetric assay,and the ROMA index was calculated.The serum tumor marker levels and positive rate of the two groups of patients and different stages of ovarian cancer were compared.The receiver operating characteristic curve(ROC)was used to analyze the diagnostic efficacy of the above markers single or combined detection on ovarian cancer and its staging.Pearson correlation test was explored to analysis the correlation between CA125 and other markers.Result1.The average age of patients with ovarian cancer and benign tumors were(55.0±12.4)and(35.8±11.5)years old(P<0.001).In the age group of 21-30 years old,31-40 years old,51-60 years old,61-70 years old,and >70 years old,the incidence of ovarian cancer and ovarian benign tumor patients was significantly different(P≦0.001),and the former 89.42%(93/104)of the patients were distributed in the >40 year old area,while the latter 65.35%(66/101)of the patients were distributed in the 40-year-old area.The ratio of FIGO III~IV patients in ovarian cancer group was about 71.2%(74/104).2.The serum levels of CA153,CA125,D-dimer and HE4 in ovarian cancer patients were significantly higher than those in benign tumors(P<0.001).Except for CA153(P=0.003),levels of tumor markers in ovarian cancer patients with stage III~IV was no significant difference to the patients with stage I~II(P>0.05).3.The positive rates of CEA,AFP,CA199,CA153,CA125,D-dimer and HE4 in the differential diagnosis of benign and malignant ovarian tumors were 5.8%,6.7%,24.0%,59.6%,84.6%,79.5%,76.7% respectively,sensitivity were 5.8%,6.7%,24.0%,59.6%,84.6%,80.7%,72.3% respectively,specificity were 100%,94.1%,77.2%,98.0%,70.3%,94.6%,100% respectively,and the AUC were 0.529,0.58,0.434,0.831,0.874,0.938,0.944 respectively.The positive rates of different stages of ovarian cancer diagnosis(III~IV)were 5.4%,6.8%,20.3%,75.7%,95.9%,93.6%,96.8% respectively,the sensitivity were 3.3%,6.7%,26.7%,86.7%,96.7%,93.3%,96.7% respectively,the specificity were 100%,86.7%,46.7%,86.7%,53.3%,73.3%,73.3% respectively,and the AUC were 0.538,0.661,0.349,0.949,0.889,0.952,0.953 respectively.4.Combined index detection includes ROMA index,CA153+D-dimer+CA125,CA125+D-dimer+HE4,CA153+D-dimer+HE4 and CA125+CA153+HE4,which presented higher positive rate(89.4%-100.0%),sensitivity(89.2-93.4%),specificity(89.7-95.6%)and AUC(0.942-0.972)than the single marker detection for the differential diagnosis of benign and malignant ovarian tumors,but the false positive rate was increased in combined detection.Uniformity,the positive rate(100.0%),sensitivity(90.3-100%),specificity(80-87.5%)and AUC(0.935-0.946)were also elevated for combined detection than the single detection,which accompanied by the increased false positive rate(68.8-100%).5.There was a significant positive correlation between CA125 and CA153,D-dimer,HE4(R=0.193,0.270,0.284,P<0.01),but no significant correlation with CEA,AFP and CA199(P>0.05).Conclusion1.In this study,six serological markers were detected.Among them,CA125,CA153,D-dimer and HE4 were used for the preoperative diagnosis and stagingdiagnosis of ovarian cancer.Serum CA125 has a positive correlation with CA153,D-dimer and HE4.The levels of CEA,AFP and CA199 were not significantly elevated in patients with ovarian cancer and could not be used as indicators for the diagnosis of ovarian cancer.Multi-index combined detection including CA125,CA153,D-dimer,HE4 and ROMA index can effectively improve the diagnostic efficiency of preoperative diagnosis and staging diagnosis of ovarian cancer,but may be accompanied by the increase and specificity of false positive rate Reduced problems;In clinical practice,a combination of patient history,serum tumor markers and imaging examination should be used to rationally select preoperative diagnostic indicators for ovarian cancer.2.Age is one of the risk factors for ovarian cancer.Ovarian cancer and benign ovarian tumors have significant differences in the incidence of different age groups.Before the age of 40,most of the ovarian benign tumors occurred.After the age of 50,the incidence of ovarian cancer was mostly.